Acoustic cues for body size: how size-related features are used and perceived

We live in a noisy world. There is no place on the Earth where it is possible to have the experience of complete silence, not even the deepest place in the ocean. Billions of living and nonliving objects around us produce sounds, which are extremely different in their physical structure. Some of these sounds are noisy, some are harmonic, some are continuous, others are impulsive, soft, loud; the sound environment contains an infinite combination of all these characteristics and more. Evolving in such an environment has resulted in a human auditory system that is able to extract useful information from sounds. We are able to say whether a sound source is still or moving (and in the latter case, the direction of movement), what kind of object produced the sound, and the meaning of the message if the perceived sound is an intentional communicative signal. When we hear someone\u2019s voice, for instance, we are able to extract useful information about talker identity apart from the meaning of the heard words. This thesis focuses on a particular kind of information that can be extracted from an acoustic signal: the apparent size of the sound-producing object

STATE AND DEVELOPMENT OF AUTOMOTIVE ACCUMULATORS

openStato e sviluppo degli accumulatori per autotrazione, analizzando la capacità ed autonomia delle batterie, la loro gestione termica, i cicli di ricarica e la loro sostenibilità delle batterie

Striatal signaling in the treatment of Parkinson's disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by typical motor symptoms that are caused by depletion of dopamine (DA) in the striatum. These symptoms are treated with the DA precursor L-DOPA, or with DA receptor (DAR) agonists. L-DOPA is the most efficacious treatment, but causes complications that limit its utility, in particular, dyskinesia (involuntary movements). Models of L-DOPA-induced dyskinesia can be obtained in rats and mice sustaining nigrostriatal DA lesions and treatment with L-DOPA. In these animal models, the induction of abnormal involuntary movements (AIMs) by L-DOPA is correlated with a large activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in striatal spiny projection neurons (SPNs).Work in the present thesis has aimed at (i) identifying molecular pathways involved in the large induction of ERK1/2 by L-DOPA (Papers I and III); (ii) optimizing rating scales to assess L-DOPA-induced dyskinesia (LID) in the mouse, to compare the efficacy of several subtype-specific DAR antagonists (Paper II); (iii) applying cell type-specific chemogenetics to determine how the two main types of SPNs contribute to therapeutic vs. dyskinetic effects of L-DOPA (Paper IV). Our results reveal that L-DOPA-induced ERK1/2 depends on an interaction between D1R and calcium-dependent pathways, which are critically modulated by metabotropic glutamate receptor type 5 (mGluR5). Antagonizing mGluR5 or its downstream effectors, such as phospholipase C (PLC), inhibits striatal ERK1/2 activation both ex vivo and in vivo. Moreover, in vivo antagonism of mGluR5 and PLC reduces D1R-dependent AIMs in rat and mouse models of dyskinesia. The same treatments do not affect dyskinesia provoked by the stimulation of D2 receptors (D2R), which is supposed to depend on striatal neurons of the indirect pathway (D2R-expressing). To dissect the contribution of D1R- and D2R-expressing neurons to dyskinesia, we used viral vector-mediated chemogenetics. The results show that both cell types contribute to LID with opposite modulatory roles. Stimulation of D1R-expressing SPNs amplifies both L-DOPA therapeutic and dyskinetic action, while activation of D2R-expressing SPNs inhibits them. Induction of AIMs is promoted by the recruitment of signaling mechanisms that mimic D1R activation. However, maximally severe AIMs are reproduced by concomitant activation of both D1R- and D2R-expressing SPNs, thus underlying the concurrent role of both pathways in the development of LID. Through the use of a novel scale for rating AIMs in the mouse model of PD, we also unraveled the anti-dyskinetic potential of several DAR antagonists. We found that antagonism of D1R, D2R, D3R and D4R reduced L-DOPA-induced AIMs with a treatment-specific anti-dyskinetic profile, thus pointing to an involvement of all DARs in the modulation of LID. Taken together, the results included in this thesis provide new insights on the signaling pathways and neural circuits through which the dopaminergic treatment of PD affects motor behaviors. Moreover, the work in this thesis contributes to methodological advances to preclinical research on PD and LID

mGlu receptors in the treatment of Parkinson's disease and L-DOPA-induced dyskinesia

Parkinson's disease (PD) is a neurodegenerative disorder characterized by typical motor features that result from dopamine (DA) depletion in the striatum. DA replacement therapy with L-DOPA is the most efficacious symptomatic treatment, but causes complications that limit its utility, in particular, L-DOPA-induced dyskinesia (LID). LID is primarily caused by pre-synaptic and post-synaptic changes in DA neurotransmission, although it also depends on altered glutamatergic transmission at several nodes of the cortico-basal ganglia-thalamocortical network. The important functional interplay between dopaminergic and glutamatergic systems has stimulated an interest in metabotropic glutamate receptors (mGluRs) as potential therapeutic targets in PD and LID. We here review the antiparkinsonian and antidyskinetic potential of modulating group I, II, and III mGluRs in several preclinical models of PD. We also provide an update on clinical trials evaluating mGluR5 or mGluR4 ligands in PD

Composition of phenolic compounds and antioxidant activity of commercial aqueous smoke flavorings

The antioxidant activity of 12 aqueous commercial smoke flavorings used in the food industry was determined by two methods: bleaching of the carotenoid crocin and scavenging of the DPPH radical. The reaction with the DPPH radical was evaluated by calculating the effective concentration (EC50) and the antiradical efficiency (AE). A gas chromatography-mass spectrometry method was, moreover, used for the determination of 2-methoxyphenols, 2,6-dimethoxyphenols, and dihydroxybenzenes. The methoxyphenols were extracted from the aqueous smoke by dichloromethane, and also the residue aqueous phase was analyzed to determine the more water-soluble dihydroxybenzenes. The recovery and the repeatability of the method are reported. The total phenolic concentrations of the smoke flavorings showed a wide range, from about 1000 to 25000 mg/kg. Considering the three classes of compounds, the concentrations were about 300\u20133000 mg/kg for the 2-methoxyphenols, 200\u201311000 mg/kg for the 2,6-dimethoxyphenols, and 140\u201310000 mg/kg for the dihydroxybenzenes. The range of the antioxidant activities of the smoke flavorings was wide, reflecting the wide range of the phenolic concentrations. Good correlations were obtained between the total phenolic concentration and the antioxidant activities determined by both the DPPH and crocin assays

Alterations of striatal indirect pathway neurons precede motor deficits in two mouse models of Huntington's disease

Striatal neurons forming the indirect pathway (iSPNs) are particularly vulnerable in Huntington's disease (HD). In this study we set out to investigate morphological and physiological alterations of iSPNs in two mouse models of HD with relatively slow disease progression (long CAG repeat R6/2 and zQ175-KI). Both were crossed with a transgenic mouse line expressing eGFP in iSPNs. Using the open-field and rotarod tests, we first defined two time points in relation to the occurrence of motor deficits in each model. Then, we investigated electrophysiological and morphological properties of iSPNs at both ages. Both HD models exhibited increased iSPN excitability already before the onset of motor deficits, associated with a reduced number of primary dendrites and decreased function of Kir- and voltage-gated potassium channels. Alterations that specifically occurred at symptomatic ages included increased calcium release by back-propagating action potentials in proximal dendrites, due to enhanced engagement of intracellular calcium stores. Moreover, motorically impaired mice of both HD models showed a reduction in iSPN spine density and progressive formation of huntingtin (Htt) aggregates in the striatum. Our study therefore reports iSPN-specific alterations relative to the development of a motor phenotype in two different mouse models of HD. While some alterations occur early and are partly non-progressive, others potentially provide a pathophysiological marker of an overt disease state

L'image du fonctionnaire dans le Canton de Genève

Quelle image les fonctionnaires du Canton de Genève ont-ils actuellement ? Comment peut-on expliquer cette image et comprendre les mécanismes qui contribuent à la façonner ? Et surtout: quelles stratégies d'action mettre en oeuvre pour l'améliorer, afin de valoriser le renouveau des services publics et contribuer à une motivation renouvelée des agents publics ? Ce cahier présente les résultats d'une recherche conduite par l'équipe du prof. Y. Emery, portant sur les fonctionnaires genevois. Par une approche originale, elle permet de confronter les visions auto-perçues (les fonctionnaires de l'Etat et de la Ville vus par eux-mêmes) et hétéro-perçues (les fonctionnaires vus par les élus et le grand public). Dans un premier temps, les données ont été recueillies par questionnaires administrés; les thèmes essentiels ont ensuite été repris lors d'entretiens en profondeur. Sur la base des tendances fortes constatées, plusieurs hypothèses sont discutées, notamment celle de " l'existence d'un mythe du fonctionnaire rond-de-cuir ". La recherche aboutit à une centaine de propositions destinées à modifier une image des fonctionnaires encore négative, en décalage avec les appréciations positives sur les qualités professionnelles et les prestations fournies par les agents du service public